miR-195 Regulates Proliferation and Apoptosis through Inhibiting the mTORp70s6k Signaling Pathway by Targeting HMGA2 in Esophageal Carcinoma Cells

Abstract EN

miR-195 is related to tumorigenesis and frequently inhibits cell proliferation and promotes apoptosis in various cancers, including esophageal carcinoma (EC).

The mTOR/p70s6k signaling pathway, which is the major target pathway for HMGA2, regulates the survival and cell proliferation of many tumors and is commonly active in EC.

The relationships of miR-195, HMGA2, and the mTOR/p70s6k signaling pathway in EC, however, remain unknown.

In the present study, we found that the miR-195 level was significantly downregulated in EC tissues, while the mRNA expressions of HMGA2 were significantly upregulated.

Dual-luciferase reporter assay demonstrated that HMGA2 is a target of miR-195.

MTT assay and flow cytometry revealed that miR-195 overexpression inhibited cell proliferation and induced apoptosis by targeting HMGA2.

We also found that HMGA2 restored the inhibitory effect of miR-195 on phosphorylation of mTOR and p70S6K.

Furthermore, rapamycin, a specific inhibitor of the mTOR/p70S6K signaling pathway, decreased the levels of Ki-67 and Bcl-2/Bax ratio, inhibited cell proliferation, and promoted apoptosis in EC cells.

In conclusion, upregulation of miR-195 significantly suppressed cell growth and induced apoptosis of EC cells via suppressing the mTOR/p70s6k signaling pathway by targeting HMGA2.